Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity

Volz, E. et al. (2021) Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity. Cell, 184(1), 64-75.e11. (doi: 10.1016/j.cell.2020.11.020) (PMID:33275900) (PMCID:PMC7674007)

Abstract

Global dispersal and increasing frequency of the SARS-CoV-2 Spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of Spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large data set, well represented by both Spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the Spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.

• Item Type: Articles
• Additional Information: EV acknowledges the MRC Centre for Global Infectious Disease Analysis MR/R015600/1. RJ and EV acknowledge funding from the European Commission (CoroNAb 101003653). VH was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) [grant number BB/M010996/1]. JTM, RMC, NJL and AR acknowledge the support of the Wellcome Trust (Collaborators Award 206298/Z/17/Z – ARTIC network). AR is supported by the European Research Council (grant agreement no. 725422 – ReservoirDOCS). DLR, ASF and ECT are supported by the MRC (MC_UU_1201412). JS was supported by the Biotechnology and Biological Sciences Research Council-funded South West Biosciences Doctoral Training Partnership [training grant reference BB/M009122/1]. TRC and NJL acknowledge support from the MRC which funded computational resources used by the project [grant reference MR/L015080/1]. TRC acknowledges funding as part of the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent projects BBS/E/F/000PR10348 and BBS/E/F/000PR10352]. AP and TRC acknowledge support from Supercomputing Wales, which is part-funded by the European Regional Development Fund (ERDF) via Welsh Government.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Shah, Dr Rajiv and Li, Dr Kathy and Robertson, Professor David and Jarrett, Professor Ruth and Jesudason, Dr Natasha and Shepherd, Dr James and Da Silva Filipe, Dr Ana and Thomson, Professor Emma and Pascall, Dr David
• Authors: Volz, E., Hill, V., McCrone, J. T., Price, A., Jorgensen, D., O'Toole, A., Southgate, J., Johnson, R., Jackson, B., Nascimento, F. F., Rey, S. M., Nicholls, S. M., Colquhoun, R. M., Da Silva Filipe, A., Shepherd, J., Pascall, D., Shah, R., Jesudason, N., Li, K., Jarrett, R., Pacchiarini, N., Bull, M., Geidelberg, L., Siveroni, I., CoG-UK Consortium, ., Goodfellow, I., Loman, N. J., Pybus, O. G., Robertson, D. L., Thomson, E. C., Rambaut, A., and Connor, T. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Cell
• Publisher: Elsevier (Cell Press)
• ISSN: 0092-8674
• ISSN (Online): 1097-4172
• Published Online: 19 November 2020
• Copyright Holders: Copyright © 2020 The Author(s).
• First Published: First published in Cell 184(1):64-75.e11
• Publisher Policy: Reproduced under a Creative Commons license